Calculus, or tartar as it is also referred to, is the solid, hard mass of calcified material deposited on and adherent to the surfaces of the teeth. Calculus is composed of inorganic salts, organic matter and water. The inorganic salts which make the calculus hard and resistant are, as shown by chemical analysis, calcium phosphates, mainly calcium hydroxyapatite, with varying, but small, amounts of other inorganic salts. Although not entirely understood, the general concept is that deposits, mostly plaque, a sticky film of oral bacteria and their products, become calcified with the ultimate formation on teeth of a hard mineral consisting of calcium hydroxyapatite (HAP).
Methods for chemically reducing or preventing calculus formation have been directed at affecting the process at any of several stages in its development. One approach is to develop agents which inhibit the formation of the crystalline calcium phosphate or hydroxyapatite. A chemical agent which would interfere with the crystal growth of hydroxyapatite would be an effective anticalculus agent.
It is well known that dissolved pyrophosphate ions are effective agents in inhibiting the crystal growth of hydroxyapatite. Even at extremely low concentrations, dissolved pyrophosphate is an effective inhibitor of hydroxyapatite formation from its amorphous phases. Draus et al (Arch. Oral Biol. 15: 893-896, 1970) demonstrated that natural pyrophosphate in saliva inhibits the conversion of amorphous calcium phosphate into hydroxyapatite. Their studies, carried out in vitro. suggested that the attachment of pyrophosphate ions to calcium results in a calcium-pyrophosphate complex which causes an inhibition of crystal growth to hydroxyapatite. Draus et al were also aware of the presence of pyrophosphatase in the saliva of subjects who were calculus formers and pointed out that pyrophosphate ions or complexes can be hydrolyzed by the enzyme to form orthophosphate ions or calcium orthophosphate which are inactive as inhibitors of hydroxyapatite formations. They suggested that dissolved pyrophosphate ions would inhibit calculus formation if the pyrophosphate could be protected from pyrophosphatase-induced hydrolysis. (For example, it has been known for some time that fluoride ion is a pyrophosphatase inhibitor. Rapp et al, J. Dent. Res. 39: 372-376, 1960; Vogel et al, Archs. Oral Biol. 12: 159-163, 1967. )
Briner et al (W. W. Briner, M. D. Francis, "In Vitro and In Vivo Evaluation of Anti-Calculus Agents". Calc. Tiss. Res. 11:10-22 (1973)) demonstrated the in vitro and in vivo anticalculus effects of dissolved pyrophosphate ions and showed that 1% solutions applied to the teeth of rats could reduce calculus severity by 38.2% and incidence by 11.7%.
In the light of these disclosures, Parran et al, in U.S. Pat. Nos. 4,515,772, 4,590,066, 4,684,518, 4,806,339, 4,885,155 and 4,999,184, have proposed as anticalculus agents dentifrices and mouthwashes containing mixtures of various alkali metal pyrophosphate salts and soluble fluorides. Parran et al claimed that those compositions capable of providing at least 1.5% of dissolved P.sub.2 O.sub.7.sup.-4 reducing calculus.
The efficacy of dentifrices containing pyrophosphate ions and sodium fluoride in preventing calculus deposits has been confirmed in many published clinical studies. For example, Lobene (Clinical Preventive Dentistry 8(3):5-7, 1986) showed that the use of a dentifrice theoretically containing 3.3% pyrophosphate ion (from 5.0% tetrasodium pyrophosphate) and 0.243% sodium fluoride resulted in a 44.2% reduction in calculus deposits after three months when compared to a placebo dentifrice containing 0.243% sodium fluoride without pyrophosphate ions. Using a dentifrice containing a similar concentration of pyrophosphate ion, Schiff (Clinical Preventative Dentistry 9(2) 13-16 (1987)) obtained a 35.5% reduction after three months and a 45.95% reduction after six months.
It has been found, however, that dentifrice compositions containing high proportions of tetrasodium pyrophosphate as the anticalculus agent, especially in the amounts used above, e.g., 5% tetrasodium pyrophosphate by weight, are gritty, and that the solid gritty particles are composed of undissolved tetrasodium pyrophosphate species. While the gritty particles in such dentifrices can be avoided by employing a predominant portion of the pyrophosphate in the form of the tetrapotassium salt, see, for example, Gaffar et al, U.S. Pat. Nos. 4,806,340 and 4,931,273, problems still exist with these compositions due to the objectionable taste of the tetrapotassium salts when used in large amounts.
It has also been proposed to add synthetic anionic polymeric polycarboxylate salts to pyrophosphate/fluoride-containing anticalculus dentifrices to further inhibit phosphatase-induced hydrolysis of pyrophosphate ions or the calcium-pyrophosphate complex formed therefrom. Thus, Gaffar et al U.S. Pat. Nos. 4,627,977, 4,806,342 and 4,869,898 disclose such formulations containing as little as 0.1% pyrophosphate, but exemplifying only formulations containing 3%, 6% and 7% by weight of tetrasodium pyrophosphate. Gaffar et al U.S. Pat. Nos. 4,806,340, 4,906,456, 4,925,654, 4,931,273 and 4,966,777 disclose the use of from 4.3% to 7% of alkali metal pyrophosphate as an anticalculus agent, at least 4.3% of which is tetrapotassium pyrophosphate and up to 2.7% of which is tetrasodium pyrophosphate. Finally, Gaffar et al U.S. Pat. No. 4,889,712 discloses the use of pyrophosphate ion in amounts below 3% by weight when it is admixed with the polycarboxylate salt in proportions of from about 0.3:1 to about 2.5:1.
The anticalculus efficacy of dentifrices containing low levels of pyrophosphate in combination with polymeric polycarboxylate was confirmed by Singh et al. (J. Clin. Dent. 53-55, 1990) and by Schiff et al. (J. Clin. Dent. 2:48-52, 1990). In these clinical studies the effect on calculus deposits of dentifrices theoretically containing 1.3% pyrophosphate ion (from 2.0% tetrasodium pyrophosphate), either alone or in admixture with 1.5% of a copolymer of methoxyethylene and maleic acid, was studied. It was found that the dentifrices containing both the soluble pyrophosphate and the carboxylate copolymer additive significantly reduced supragingival calculus formation after an initial oral prophylaxis, to the extent of about 29% to 36% in excess of the results obtained by use of placebo dentifrices absent such materials. On the other hand, it was concluded that dentifrices containing 1.3% soluble pyrophosphate but no carboxylate copolymer did not significantly reduce supragingival calculus formation.
One problem with the addition of carboxylate copolymers to dentifrices, however, is that many people find the slick feeling on the teeth and in the mouth, due to the presence of polymer residue after brushing, to be unpleasant.
Accordingly, in spite of the many disclosures dealing with the use of pyrophosphates as oral anticalculus agents, the need for improved anticalculus dentifrices still exists.
It is among the objects of this invention, therefore, to provide improved anticalculus dentifrices which will not be subject to one or more of the above problems and disadvantages.
Other objects and advantages will appear as the description proceeds.